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Cytadren (Aminoglutethimide) - Drug Interactions, Contraindications, Overdosage, etc

 
 



DRUG INTERACTIONS

Drug Interactions

Cytadren accelerates the metabolism of dexamethasone; therefore, if glucocorticoid replacement is needed, hydrocortisone should be prescribed.

   Aminoglutethimide diminishes the effect of coumarin and warfarin.

OVERDOSAGE

Acute Toxicity

No deaths due to overdosage with Cytadren have been reported.

   The highest known doses that have been survived are 7 g (33-year-old woman), 7.5-10 g (16-year-old girl), and 10 g (10-year-old boy).

   Oral LD50’s (mg/kg): rats, 1800; dogs, >100. Intravenous LD50’s (mg/kg): rats, 156; dogs, >100.

Signs and Symptoms

An acute overdose with Cytadren may reduce the production of steroids in the adrenal cortex to a degree that is clinically relevant. The following manifestations may be expected:

    Respiratory Function: Respiratory depression, hypoventilation.

    Cardiovascular System: Hypotension, hypovolemic shock due to dehydration.

    Central Nervous System/Muscles: Somnolence, lethargy, coma, ataxia, dizziness, fatigue. (Extreme weakness has been reported with divided doses of 3 g daily.)

    Gastrointestinal System: Nausea, vomiting.

    Renal Function: Loss of sodium and water.

    Laboratory Findings: Hyponatremia, hypochloremia, hyperkalemia, hypoglycemia.

   The signs and symptoms of acute overdosage with Cytadren may be aggravated or modified if alcohol, hypnotics, tranquilizers, or tricyclic antidepressants have been taken at the same time.

Treatment

Symptomatic treatment of overdosage is recommended.

   Since aminoglutethimide and glutethimide are chemically related, measures that have been used in successfully removing glutethimide from the body might be useful in removing aminoglutethimide.

   Gastric lavage and unspecified supportive treatment have been employed. Full consciousness following deep coma was regained 40 hours or less after ingestion of 3 or 4 g without lavage. No evidence of hematologic, renal, or hepatic effects was subsequently found.

   Close monitoring should be provided, and appropriate measures taken to support vital functions, if necessary.

   If deficiency of circulating glucocorticoid develops, an intravenous infusion of a soluble hydrocortisone preparation (100 mg of hydrocortisone sodium succinate in 500 mL of isotonic sodium chloride solution) and 50 mL of 40% glucose solution should be given within 3 hours. After the initial infusion is completed, an intravenous administration of hydrocortisone, 10 mg per hour, should be continued until the patient is able to take oral cortisone.

   If hypovolemia or hypotension occurs, an intravenous administration of norepinephrine, 10 mg, in 500 mL of isotonic sodium chloride should be administered according to the patient’s needs and response. After rehydration, 500 mL of plasma or blood should be given for maintenance of sufficient circulatory volume.

   Dialysis may be considered in severe intoxication.

CONTRAINDICATIONS

Cytadren is contraindicated in those patients with serious forms, and/or more severe manifestations, of hypersensitivity to glutethimide or aminoglutethimide.

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